Method for roll coating multiple stents

ABSTRACT

An improved method and apparatus for high-volume production of coated stents with highly uniform stent coatings using a roll coating technique is provided. In a first embodiment, uncoated stents are placed onto rotating stent holders with automated stent handling equipment. The holders are mounted on an endless conveyer belt which advances the stents toward a stent coater. As the stents advance through the coater, the holders rotate, thereby rolling the stents about their longitudinal axes as coating material is sprayed toward them, ensuring the stents are uniformly coated on their exterior and interior surfaces. After the conveyer turns to carry the coated stents back toward the loading area, the rotating stents pass again through the coating spray, downstream of the initial coating location, thereby increasing the efficient utilization of the coating material. The conveyer then advances the coated stents to an unloading area for removal before the holders return to the stent loading area to receive new stents.

FIELD OF THE INVENTION

The present invention generally regards the holding of stents duringmanufacture to enable the application of therapeutic and/or protectivecoatings. More specifically, the present invention pertains to a methodfor high-throughput, efficient and uniform coating of stents, whereinthe stents placed on rotating fixtures on a conveyer, and the conveyerpasses the rotating stents through a coating spray or immersion bath toapply a coating to the stents.

BACKGROUND

Medical implants are used for innumerable medical purposes, includingthe reinforcement of recently re-enlarged lumens, the replacement ofruptured vessels, and the treatment of disease such as vascular diseaseby local pharmacotherapy, i.e., delivering therapeutic drug doses totarget tissues while minimizing systemic side effects. Such localizeddelivery of therapeutic agents has been proposed or achieved usingmedical implants which both support a lumen within a patient's body andplace appropriate coatings containing absorbable therapeutic agents atthe implant location.

The delivery of expandable stents is a specific example of a medicalprocedure that involves the deployment of coated implants. Expandablestents are tube-like medical devices, typically made from stainlesssteel, Tantalum, Platinum or Nitinol alloys, designed to be placedwithin the inner walls of a lumen within the body of a patient. Thesestents are typically maneuvered to a desired location within a lumen ofthe patient's body and then expanded to provide internal support for thelumen. The stents may be self-expanding or, alternatively, may requireexternal forces to expand them, such as by inflating a balloon attachedto the distal end of the stent delivery catheter.

Because of the direct contact of the stent with the inner walls of thelumen, stents have been coated with various compounds and therapeuticagents to enhance their effectiveness. These coatings may, among otherthings, be designed to facilitate the acceptance of the stent into itsapplied surroundings. Such coatings may also be designed to facilitatethe delivery of one of the foregoing therapeutic agents to the targetsite for treating, preventing, or otherwise affecting the course of adisease or tissue or organ dysfunction.

Where the stent has been coated, care must be taken during itsmanufacture and delivery within the patient to ensure the coating isevenly applied and firmly adherent to the stent, and further that thecoating is not damaged or completely removed from the implant during thedeployment process. When the amount of coating is depleted the implant'seffectiveness may be compromised and additional risks may be inured intothe procedure. For example, when the coating of the implant includes atherapeutic, if some of the coating were removed during deployment, thetherapeutic may no longer be able to be administered to the target sitein a uniform and homogenous manner. Thus, some areas of the target sitemay receive high quantities of therapeutic while others may receive lowquantities of therapeutic. Similarly, if the therapeutic is ripped fromthe implant it can reduce or slow down the blood flowing past it,thereby, increasing the threat of thrombosis or, if it becomesdislodged, the risk of embolisms. In certain circumstances, the removaland reinsertion of the stent through a second medical procedure may berequired where the coatings have been damaged or are defective.

The mechanical process of applying a coating onto a stent may beaccomplished in a variety of ways, including, for example, the sprayingof the coating substance onto the stent and so-called spin-dipping,i.e., dipping a spinning stent into a coating solution to achieve thedesired coating. Common to these processes is the need to apply thecoating in a uniform manner to ensure an intact, robust coating of thedesired thickness is formed on the stent. In order to achieve thedesired uniform and complete coating, it has been common for the stentsto be handled individually, with each stent separately loaded onto astent holder and the coating applied to the stent before the next stentis coated. This individual handling typically has resulted in lowproduction rates of coated stents. A further disadvantage of these priorstent coating processes is that, because the stents are wire meshstructures with substantial void area between the mesh wires, theutilization of the stent coating material sprayed toward the stents isvery low. For example, in some cases the amount of stent coating sprayedtoward the stent which actually adheres to the stent mesh is less thanfive percent.

Thus, there is a need for a method for coating stents which efficientlyapplies the stent coating material in a manner that results in a highquality, uniform coating on the stents at high coated stent productionrates.

SUMMARY OF THE INVENTION

The present invention is directed to a method for overcoming theforegoing disadvantages. Specifically, in a first step of a firstembodiment of the method, stents are loaded with high speed stenthandling equipment onto rotating pins that are mounted to an endlessconveyer belt. In a second step, while the stents are rolling abouttheir longitudinal axes atop the rotating pins, stent coating materialis applied as the endless belt advances the stents through a stentcoater containing a coating sprayer. As the stents are returned towardthe stent loading area by the endless belt, they receive additionalcoating material from the coating sprayer as they pass a second timethrough the coating spray downstream of the initial coating location.The coated stents are then removed from their holders before the endlessbelt returns the stent holders to the stent loading area to receive newuncoated stents.

A number of alternative embodiments for performance of the method of thepresent invention are envisioned. For example, there may be a number ofalternative embodiments for performing the stent placement step, such asproviding stents pre-mounted on stent holders with rotating pinsequipping with corresponding stent holder receivers to facilitate stenthandling by automated stent placement equipment. Similarly, in the stepof applying the coating material, rather than spraying the coatingmaterial perpendicularly across the endless belt, the coating may beapplied from a sprayer aligned with the major axis of the endless beltsuch that the rolling stents have a longer exposure to the coatingspray. The sprayer may also apply the coating while the spray head isrotating about the line of rolling stents. In a further embodiment, thecoating application step may be performed by drawing the rolling stentsthrough a coating bath. Other embodiments extend the stent coating stepto include the endless belt reversing direction several times to causethe rolling stents to pass several times through the downstream portionsof the coating spray to improve coating material utilization, and theinclusion of additional stent processing steps between the coatingapplication step and the coated stent unloading step, such asaccelerating the drying of the stent coating by advancing the coatedstents through an infrared coating dryer.

The result of the various foregoing embodiments of the method of thepresent invention is high volume, efficient and lower-cost production ofstents with a highly uniform coating on their exterior and, in desired,interior surfaces.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic overhead view of a stent coating process inaccordance with an embodiment of the method the present invention.

FIG. 2 is a side view showing a stent and the upper portion of arotating pin on which the stent is placed in accordance with the methodof the present invention.

FIG. 3 is a side illustration of stent-bearing rotating pins mounted ona conveyer belt in accordance with the method of the present invention.

FIG. 4 is an overhead view of the stent-bearing rotating pins andconveyer belt shown in FIG. 3 in accordance with the method of thepresent invention.

FIG. 5 is a schematic overhead view of the stent-bearing rotating pinsand conveyer belt shown in FIG. 3 illustrating an alternative approachfor the step of applying the stent coating in accordance with the methodof the present invention.

FIG. 6 are schematic side views of alternative stent holders androtating pin mounts for engaging and holding stent holders forperforming the step of placing the stents on the conveyer in accordancewith the method of the present invention.

FIG. 7 is a schematic side view of the stent-bearing rotating pins andconveyer belt shown in FIG. 3 showing an alternative approach to thestep of applying the stent coating by immersing the stents into acoating bath in accordance with the method of the present invention.

DETAILED DESCRIPTION

The present invention is directed to a method for overcoming theforegoing disadvantages by applying a stent coating to stents that arebeing rolled about their longitudinal axis, where the stents are loadedonto rotating holders affixed to a conveyer, and the conveyer carriesthe rotating stents and holders through a coating applicator one or moretimes.

The method of the present invention in a first embodiment is as follows.In this first embodiment, a conveyer in the form of an endless belt 1 isarranged around a first pulley 2 at a first end 3 of the belt and asecond pulley 4 at a second, opposite end 5 of the belt. Endless belt 1may be advanced by rotating either pulley 2 or pulley 4. Backing plates6 are provided in the region between pulleys 2 and 4. The backingplates, which can be located adjacent to either the inner or outer faceof the belt, are arranged to contact outer peripheral edges of rotatingpins 7 mounted on endless belt 1 (details of rotating pins 7 and theirmounting are discussed further, below). When endless belt 1 is advanced,the friction between the outer peripheral portions of rotating pins 7and backing plates 6 causes the pins to rotate.

As a first step of the method in this embodiment, stents 8 are placedwith automated stent placement equipment (not illustrated) onto rotatingpins 7 as endless belt 1 is advanced. In this embodiment, the stents areloaded onto the rotating pins near the first end 3 of the endless belt,and advance toward second end 5 as endless belt 1 advances. In FIG. 1,the freshly loaded, uncoated stents are on endless belt 1 on the lowerside of the illustration, moving from first end 3 toward second end 5.At a location along endless belt 1 separate from the stent loadinglocation, a stent coater 9 is positioned such that it dispenses a stentcoating spray toward endless belt 1 when activated. In this embodiment,stent coater 9 includes a stent coating sprayer 10 located near secondend 5 which sprays the coating material generally perpendicularly acrossendless belt 1. The stent coater may further include a housing (notillustrated) to contain and potentially reclaim coating overspray.

In the second step of the method in this first embodiment, endless belt1 is advanced to cause stents 8 to roll about their longitudinal axes astheir respective pins 7 rotate (due to the pins' frictional engagementwith backing plate 6). As endless belt 1 advances, the rolling stents 8are simultaneously carried along the path of endless belt 1 into and outof the stent coater. The step of applying the stent coating to thestents is performed by causing coating sprayer 10 to dispense the stentcoating onto stents 8 as they pass through the stent coater. Further,because endless belt 1 reverses direction at pulley 4, stent coatingspray that passes by or through the stents moving toward second end 5can be utilized to apply additional coating material to the stents asthey pass from second end 5 back toward first end 3, therebysubstantially improving the efficiency of the coating process. Finally,as the coated stents 8 approach first end 3, they are removed from theirrespective rotating pins 7 by automated stent removal equipment (notillustrated), prior to the rotating pins' return to the stent loadingarea for loading of new uncoated stents.

The rotating pins 7 in this embodiment, and their relationship toendless belt 1, backing plates 6 and stents 8, are now furtherdescribed. FIG. 2 illustrates a schematic view of the upper portion of arotating pin 7 and its relationship to stent 8. When placed ontorotating pin 7, stent 8 is oriented with its longitudinal axis generallyin line with the longitudinal axis of a rotating pin 7. Rotating pin 7is sized such that when stent 8 is placed over the top of pin 7, thestent is supported by pin 7 in a manner which ensures that stent 8rotates with pin 7 when the pin is rotated around its longitudinal axis.In this embodiment, rotating pin 7 has a radial extension or shelf 11upon which stent 8 rests when placed over the top of pin 7.Alternatively, rotating pin 7 may have a tapered shape, such that theinner diameter of stent 8 rests directly upon the tapered sides of pin7. Rotating pin 7 is preferably configured such that its protrusion intothe interior annular region of stent 8, while sufficient to ensure stent8 is retained on the pin during its transit through stent coatingapplicator 9, is minimized in order to minimize the extent to which pin7 interferes with the application of the coating spray to the innersurface of stent 8.

FIG. 3 shows the general arrangement of rotating pins 7 and stents 8 onendless belt 1 in the first embodiment. In both FIG. 3 a and FIG. 3 b,stents 8 rest on the tops of rotating pins 7, which are in turn rotablyheld on belt 1. Any of a variety of conveyer arrangements well known inthe art may be used to rotably hold pins 7. In this embodiment, the pinsare held by belt links 12 of endless belt 1. The belt links 12 may bearranged any suitable manner that permits the pins 7 to rotate abouttheir longitudinal axes as the belt advances, such as with interlockingfingers or hooks 13 on the ends of the links which cooperate with thepins 7 and an adjacent link to effectively use rotating pins 7 as hingepins in the endless belt, as illustrated in FIG. 3 a. Alternatively,endless belt 1 may be an endless rubber belt to which are mountedU-shaped brackets which loosely capture rotating pins 7 between the beltand the brackets, as illustrated in FIG. 3 b.

In order to provide for the rotation of rotating pins 7 as endless belt1 advances, a flange 14 is provided in this embodiment on each rotatingpin 7. As shown in the overhead view in FIG. 4, flange 14 is ofsufficient radius that its outer periphery is in rolling contact withbacking plates 6 as endless belt 1 advances, thereby causing pins 7 andtheir respective, stents 8 to roll about their longitudinal axes as belt1 advances. Flange 14 may be provided above, below, or in a gap through,endless belt 1, as desired to provide positive engagement of flanges 14against backing plates 6. As those of skill in the art will readilyrecognize, a variety of alternative means other than backing plates 6may be provided to cause rotating pins 7 to roll stents 8, such asgear-drive of the rotating pins, so as long as the desired rotation ofstents 8 is obtained. Alternatively, rotating pins 7 may be rotated bymeans that are independent of the means that advance endless belt, forexample, by a separate electric motor.

The diameter of flange 14 and the speed of advance of endless belt 1 areadjusted as necessary to ensure an optimal stent coating is obtained.This requires stents 8 to be rotated at a rate that is slow enough toensure effective coverage of outer and inner portions of stent 8 bysprayer 10 as the stents traverse through the coating spray, but fastenough to ensure that the stents make at least one complete revolutionwhile stent 8 is within the spray pattern from sprayer 10. An endlessbelt advance speed of 0.1-10 cm per second and a stent rotation rate of10-100 degrees per second may be used to obtain satisfactory coating ofstents with the foregoing roll coating method.

In addition to executing the step of applying the coating to the stents8 using a spray applicator aligned perpendicular to the direction ofadvance of endless belt 1, a number of alternative spray configurationscan be envisioned. For example, in order to minimize the interference ofrotating pins 7 with the application of the coating to the inner surfaceof stents 8, coating sprayer 10 may be elevated above endless belt 1 andaligned to dispense the coating spray downward at an angle toward therolling stents 8. As shown in FIG. 5, coating sprayer 10 could also belocated above endless belt 1 and aligned with the belt such that itsprays in the direction of stent travel and thus has an extendedopportunity to apply the coating to the stents. In a further alternativesprayer embodiment, the coating sprayer may be provided on means such asa rotating arm that permits the sprayer to rotate around the rollingstents as they are advanced on the conveyer. Performing the coatingapplication step in this embodiment provides further assurance a uniformcoating will be obtained at high coated stent production levels.

An additional embodiment of the present method includes multipledirection reversals of endless belt 1 downstream of coating sprayer 10such that stents 8 re-enter the spray dispensed from sprayer 10 severaltimes before belt 1 returns to a stent removal station. By expanding thecoating application step in this manner, this embodiment provides forenhanced coating efficiency as each pass of stents 8 through thedownstream portions of the coating spray further improves theutilization of the sprayed coating and thereby improves coatingefficiency.

A further advantage of the foregoing method is that after the step ofapplying the coating to the rolling stents, there may be providedadditional steps which enhance high volume coated stent production. Anexemplary further embodiment of the present method thus may include thestep of passing the stents through a coating dryer (such as an infraredheater) following the application of the coating, wherein the rollingstents present all their coated surfaces to the dryer for even,accelerated drying prior to removal from their respective rotating pins7. Alternatively, the conveyer and/or the stent holder may be heated toaccelerate coating drying rates before the stents are removed from theconveyer.

In the foregoing first embodiment, the stents are placed on rotatingpins with upper portions that are shaped to directly receive the stents.Alternatively, in the first step of the present high-volume coatingmethod process, the stents may be supplied for loading onto endless belt1 already mounted on individual stent holders, where the upper portionof rotating pins 7 is adapted to grasp one end of the holder. FIG. 6shows three example stent holder and cooperating rotating pinarrangements which are amenable to high-volume automated stent placementand removal operations. In FIG. 6 a, stent 8 is mounted on stent holder15. Stent holder 15 in turn is locked within a bayonet-type receivingportion 16 on top of rotating pin 7, where an extension 17 of stentholder 15 has been inserted into receiving portion 16 and rotated tolock the stent holder in place. Similarly, FIG. 6 b illustrates anotherstent holder 15 formed from a nitinol wire that holds stent 8 by springforce at contact points on the stent's inner surface, where receivingportion 16 is a spring-loaded clamp that grasps one end of stent holder15. FIG. 6c shows a further exemplary embodiment, wherein stent holder15 is a wire frame with triangular ends 18, stent 8 is held under alight compressive force between the ends 18, and extension 17 from stentholder 15 is a wire that is placed into the receiving portion 16 ofrotating pin 7 (in this case, a hole drilled into the top of pin 7).FIG. 6 d shows another exemplary embodiment, wherein stent holder 15 isan inflatable balloon that lightly presses against the inner surface ofstent 8 and is held, in this embodiment, in a receiving portion 16 thatgrasps one end of the stent holder balloon 15.

It should be understood that the foregoing description of variousexemplary embodiments of possible stent holders and mating receivingmounts is not intended to be limiting, and a number of modifications andalternatives may be employed that would facilitate the performance ofthe present stent coating method at high production levels. Further,alternative coating and drying step arrangements may be employed, suchas feeding the stents through multiple coating and drying cycles toapply a plurality of coats of coating material before the completedcoated stent is removed from its stent holder, or conveying the stentsthrough a plurality of coating sprayers spraying a plurality ofdifferent coatings, with or without drying periods between the coatinglayer applications.

The foregoing alternative approaches to the stent placement step, whichpositively constrain stents 8 to remain mounted on rotating pins 7,facilitate a further embodiment of the present method. In thisembodiment, rather than performing the step of applying the stentcoating by using a stent coating sprayer, the coating may be applied byadvancing endless belt 1 through a stent coating bath 19, asschematically illustrated in FIG. 7. It should be apparent to those ofskill in the art that while positive control of rolling stents 8 on thetop of rotating pins 7 is not a necessary prerequisite to use of acoating bath, use of the foregoing alternative stent holders coupled tothe rotating pins enhances the control of the stents as they passthrough coating bath 19. It should be further noted that while endlessbelt 1 is shown in FIG. 7 as being turned to a horizontal position topass through coating bath 19, no orientation limitations are intended tobe implied by the foregoing description, as a number of modificationsand equivalent alternative arrangements are possible. For example,endless belt 1 may be arranged above the coating bath and located suchthat stents 8 are held and rotated about their longitudinal axes belowbelt 1, such that only the stents and their holders pass through thecoating bath during the coating application step.

The term “therapeutic agent” as used herein includes one or more“therapeutic agents” or “drugs.” The terms “therapeutic agents” and“drugs” are used interchangeably herein and include pharmaceuticallyactive compounds, nucleic acids with and without carrier vectors such aslipids, compacting agents (such as histones), virus (such as adenovirus,andenoassociated virus, retrovirus, lentivirus and α-virus), polymers,hyaluronic acid, proteins, cells and the like, with or without targetingsequences.

Specific examples of therapeutic agents used in conjunction with thepresent invention include, for example, pharmaceutically activecompounds, proteins, cells, oligonucleotides, ribozymes, anti-senseoligonucleotides, DNA compacting agents, gene/vector systems (i.e., anyvehicle that allows for the uptake and expression of nucleic acids),nucleic acids (including, for example, recombinant nucleic acids; nakedDNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector orin a viral vector and which further may have attached peptide targetingsequences; antisense nucleic acid (RNA or DNA); and DNA chimeras whichinclude gene sequences and encoding for ferry proteins such as membranetranslocating sequences (“MTS”) and herpes simplex virus-1 (“VP22”)),and viral, liposomes and cationic and anionic polymers and neutralpolymers that are selected from a number of types depending on thedesired application. Non-limiting examples of virus vectors or vectorsderived from viral sources include adenoviral vectors, herpes simplexvectors, papilloma vectors, adeno-associated vectors, retroviralvectors, and the like. Non-limiting examples of biologically activesolutes include anti-thrombogenic agents such as heparin, heparinderivatives, urokinase, and PPACK (dextrophenylalanine proline argininechloromethylketone); antioxidants such as probucol and retinoic acid;angiogenic and anti-angiogenic agents and factors; agents blockingsmooth muscle cell proliferation such as rapamycin, angiopeptin, andmonoclonal antibodies capable of blocking smooth muscle cellproliferation; anti-inflammatory agents such as dexamethasone,prednisolone, corticosterone, budesonide, estrogen, sulfasalazine,acetyl salicylic acid, and mesalamine; calcium entry blockers such asverapamil, diltiazem and nifedipine;antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel,5-fluorouracil, methotrexate, doxorubicin, daunorubicin, cyclosporine,cisplatin, vinblastine, vincristine, epothilones, endostatin,angiostatin and thymidine kinase inhibitors; antimicrobials such astriclosan, cephalosporins, aminoglycosides, and nitorfurantoin;anesthetic agents such as lidocaine, bupivacaine, and ropivacaine;nitric oxide (NO) donors such as lisidomine, molsidomine, L-arginine,NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NOadducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, anRGD peptide-containing compound, heparin, antithrombin compounds,platelet receptor antagonists, anti-thrombin antibodies, anti-plateletreceptor antibodies, enoxaparin, hirudin, Warafin sodium, Dicumarol,aspirin, prostaglandin inhibitors, platelet inhibitors and tickantiplatelet factors; vascular cell growth promotors such as growthfactors, growth factor receptor antagonists, transcriptional activators,and translational promotors; vascular cell growth inhibitors such asgrowth factor inhibitors, growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bifunctional molecules consisting of a growth factor and acytotoxin, bifunctional molecules consisting of an antibody and acytotoxin; cholesterol-lowering agents; vasodilating agents; agentswhich interfere with endogeneus vascoactive mechanisms; survival geneswhich protect against cell death, such as anti-apoptotic Bc1-2 familyfactors and Akt kinase; and combinations thereof. Cells can be of humanorigin (autologous or allogenic) or from an animal source (xenogeneic),genetically engineered if desired to deliver proteins of interest at theinsertion site. Any modifications are routinely made by one skilled inthe art.

Polynucleotide sequences useful in practice of the invention include DNAor RNA sequences having a therapeutic effect after being taken up by acell. Examples of therapeutic polynucleotides include anti-sense DNA andRNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA toreplace defective or deficient endogenous molecules or interfering RNAsequences. The polynucleotides can also code for therapeutic proteins orpolypeptides. A polypeptide is understood to be any translation productof a polynucleotide regardless of size, and whether glycosylated or not.Therapeutic proteins and polypeptides include as a primary example,those proteins or polypeptides that can compensate for defective ordeficient species in an animal, or those that act through toxic effectsto limit or remove harmful cells from the body. In addition, thepolypeptides or proteins that can be injected, or whose DNA can beincorporated, include without limitation, angiogenic factors and othermolecules competent to induce angiogenesis, including acidic and basicfibroblast growth factors, vascular endothelial growth factor, hif-1,epidermal growth factor, transforming growth factor α and β,platelet-derived endothelial growth factor, platelet-derived growthfactor, tumor necrosis factor α, hepatocyte growth factor and insulinlike growth factor; growth factors; cell cycle inhibitors including CDKinhibitors; anti-restenosis agents, including p15, p16, p18, p19, p21,p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase (“TK”) andcombinations thereof and other agents useful for interfering with cellproliferation, including agents for treating malignancies; andcombinations thereof. Still other useful factors, which can be providedas polypeptides or as DNA encoding these polypeptides, include monocytechemoattractant protein (“MCP-1”), and the family of bone morphogenicproteins (“BMP's”). The known proteins include BMP-2, BMP-3, BMP-4,BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11,BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP'sare any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimericproteins can be provided as homodimers, heterodimers, or combinationsthereof, alone or together with other molecules. Alternatively or, inaddition, molecules capable of inducing an upstream or downstream effectof a BMP can be provided. Such molecules include any of the “hedgehog”proteins, or the DNA's encoding them.

While the present invention has been described with reference to whatare presently considered to be preferred embodiments thereof, it is tobe understood that the present invention is not limited to the disclosedembodiments or constructions. On the contrary, the present invention isintended to cover various modifications and equivalent arrangements. Inaddition, while the various elements of the disclosed invention aredescribed and/or shown in various combinations and configurations, whichare exemplary, other combinations and configurations, including more,less or only a single embodiment, are also within the spirit and scopeof the present invention.

1-21. (canceled)
 22. A method for coating stents, comprising the stepsof: placing a plurality of stents on a plurality of stent holders,wherein the stent holders are attached to a conveyer; turning the stentholders while the conveyer moves the stents; and applying a coating tothe turning stents as the stents pass through a coater.
 23. The methodof coating stents of claim 22, wherein the step of turning the stentholders while the conveyer moves the stents includes revolving the stentholders around a point.
 24. The method of coating stents of claim 22,wherein the step of turning the stent holders while the conveyer movesthe stents includes pivoting the stent holders.
 25. The method ofcoating stents of claim 22, wherein the stent holders are removablyattached to a conveyer.
 26. The method of coating stents of claim 22,wherein the conveyer is an endless belt, and the endless belt is movingas the plurality of stents is placed on the plurality of stent holders.27. The method of coating stents of claim 26, wherein the coaterincludes a coating sprayer, and the conveyer moves the plurality ofstents through a coating spray released from the coating sprayer. 28.The method of coating stents of claim 26, wherein the coater includes acoating bath, and the conveyer moves the plurality of stents through thecoating bath.
 29. The method of coating stents of claim 27, wherein thestep of applying a coating further comprises: passing the stents throughthe coating spray at a first distance from the sprayer, then passing thestents through the coating spray at a second distance from the sprayer.30. The method of coating stents of claim 26, wherein the step ofplacing a plurality of stents on a plurality of stent holders isperformed with an automated stent loader.
 31. The method of coatingstents of claim 26, wherein the stent holders are revolving basesadapted to receive individual stent handling devices on which at leastone stent is pre-mounted, and wherein the step of placing the stents onthe stent holders further comprises: placing stents pre-mounted on stenthandling devices onto the stent holders by engaging the stent handlingdevices with the revolving bases.
 32. The method of coating stents ofclaim 27, wherein the coating sprayer sprays the stent coating towardthe stents from a plurality of directions.
 33. The method of coatingstents of claim 22, further comprising the step of: drying the coatedstents prior to removal of the coated stents from the stent holders. 34.A system for coating medical devices comprising: a plurality of holdersfor holding a plurality of medical devices to be coated; a conveyer; ameans for advancing the conveyer; a means for turning the plurality ofholders; and a coater; wherein the plurality of holders is attached to aconveyer, and wherein the means for turning the holder turns theplurality of holders and medical devices while the conveyer moves themedical devices through the coater, so that a coating is applied to theturning medical devices as the medical devices pass through the coater.35. The system of claim 34, wherein at least one of the plurality ofholders is adapted to receive each of the plurality of medical devices.36. The system of claim 34, wherein the means for turning the pluralityof holders is a backing plate.
 37. The system of claim 36, wherein theplurality of holders is adapted to cooperate with the backing plate, sothat the plurality of holders turns upon contact with the backing plateas the conveyer is advanced.
 38. The system of claim 34, wherein themeans for turning the plurality of holders is a gear mechanism.
 39. Thesystem of claim 34, further comprising a dryer.
 40. The system of claim34, wherein the medical devices are stents.
 41. A system for coatingstents comprising: a plurality of stent holders for holding a pluralityof stents to be coated; a conveyer; a means for advancing the conveyer;a means for rotating the plurality of stent holders; and a coater;wherein the conveyer is an endless belt; and wherein the plurality ofstent holders is attached to the conveyer, and wherein the means forrotating the holder rotates the plurality of holders and stents whilethe conveyer moves the stents through the coater, so that a coating isapplied to the rotating stents as the stents pass through the coater.